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First published online 12 April 2006
doi: 10.1242/dev.02349

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Tracing the first waves of lymphopoiesis in mice

¹ Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
² Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
³ INSERM U506, Hopital Paul Brousse, 94807 Villejuif, France.
⁴ Department of Immunology, University of Toronto, Sunnybrook and Women's Research Institute, Toronto, ON M4N 3M5, Canada.
⁵ University of Pittsburgh and Children's Hospital, Rangos Research Center, Pittsburgh, PA 15213, USA.

^* Author for correspondence (e-mail: kincade{at}omrf.ouhsc.edu)

Accepted 8 March 2006

RAG1/GFP knock-in mice were used to precisely chart the emergence and expansion of cells that give rise to the immune system. Lymphopoietic cells detectable in stromal co-cultures arose as early as E8.5, i.e. prior to establishment of the circulation within the paraaortic splanchnopleura (P-Sp). These cells were Tie2⁺ RAG1^- CD34^Lo/- Kit⁺ CD41^-. While yolk sac (YS) also contained lymphopoietic cells after E9.5, CD41⁺ YS cells from 25-somite embryos produced myelo-erythroid cells but no lymphocytes. Notch receptor signaling directed P-Sp cells to T lymphocytes but did not confer lymphopoietic potential on YS cells. Thus, definitive hematopoiesis arises in at least two independent sites that differ in lymphopoietic potential. Expression of RAG1, the earliest known lymphoid event, first occurred around E10.5 within the embryos. RAG1/GFP⁺ cells appeared in the liver at E11.0 and progenitors with B and/or T lineage potential were enumerated at subsequent developmental stages.

Key words: Para-aortic splanchnopleura/aorta-gonad-mesonephros, Yolk sac, Thymus, Liver, Mouse

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